An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates

Jermaine Goveia, Katerina Rohlenova, Federico Taverna, Lucas Treps, Lena Christin Conradi, Andreas Pircher, Vincent Geldhof, Laura P.M.H. de Rooij, Joanna Kalucka, Liliana Sokol, Melissa García-Caballero, Yingfeng Zheng, Junbin Qian, Laure Anne Teuwen, Shawez Khan, Bram Boeckx, Els Wauters, Herbert Decaluwé, Paul De Leyn, Johan VansteenkisteBirgit Weynand, Xavier Sagaert, Erik Verbeken, Albert Wolthuis, Baki Topal, Wouter Everaert, Hanibal Bohnenberger, Alexander Emmert, Dena Panovska, Frederik De Smet, Frank J.T. Staal, Rene J. Mclaughlin, Francis Impens, Vincenzo Lagani, Stefan Vinckier, Massimiliano Mazzone, Luc Schoonjans, Mieke Dewerchin, Guy Eelen, Tobias K. Karakach, Huanming Yang, Jian Wang, Lars Bolund, Lin Lin, Bernard Thienpont, Xuri Li*, Diether Lambrechts, Yonglun Luo, Peter Carmeliet

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse), and models (in vivo/in vitro) remains poorly inventoried at the single-cell level. We single-cell RNA (scRNA)-sequenced 56,771 endothelial cells from human/mouse (peri)-tumoral lung and cultured human lung TECs, and detected 17 known and 16 previously unrecognized phenotypes, including TECs putatively regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a putative basement-membrane remodeling breach phenotype. Tip TEC signatures correlated with patient survival, and tip/breach TECs were most sensitive to vascular endothelial growth factor blockade. Only tip TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-sequenced data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen modification as a candidate angiogenic pathway.

Original languageEnglish (US)
Pages (from-to)21-36.e13
JournalCancer Cell
Volume37
Issue number1
DOIs
StatePublished - Jan 13 2020

Keywords

  • angiogenesis
  • anti-angiogenic therapy
  • cancer
  • endothelial cells
  • endothelial heterogeneity
  • multi-omics
  • single-cell RNA sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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